Project Summary/Abstract This proposal requests funding for a Lavision Biotec Ultramicroscope II. This will be the first lightsheet microscope to be made available at a core facility at Stanford University. The microscope will fill a demonstrated unmet need for large-scale imaging of cleared tissue at single-cell resolution. It will be installed at the Neuroscience Microscopy Service, a university- wide service center open to all researchers at Stanford University. The investigators that constitute the Major and Minor User groups in this application are poised to apply this instrument along with the latest tissue clearing protocols and cell-specific fluorescent-labeling tools in their NIH-funded research programs. Together, they are striving to make significant advances across a broad range of biomedical research, including: ? neuroscience, with investigations of: o the functional role of microglia in brain development. o mapping of cell-type-specific hypothalamic afferents. o regeneration of the optic nerve and optic tract after injury. o mapping recovery from the effects of early visual deprivation in mouse models by re-induction of molecular drivers of synaptic plasticity in adulthood. o post-stroke recovery mechanisms in the cortex. o mapping of activity perturbations in mouse models of neuro-degenerative disease and neurodevelopmental disorders. o detailed correlation of MRI diffusion-tensor imaging signals with neuronal fiber anatomy. ? stem cell biology: o with a study to characterize the bone marrow niche of long-term hematopoietic stem cells. ? developmental biology: o with studies of the growth and development of blood vessels in the lung. The placement of this instrument in a well-established, highly successful service center open to all researchers at Stanford insures that, over the life of this instrument, it will be used by hundreds of researchers from many tens of labs to support similarly excellent research to better understand and combat disease.